People with metabolic syndrome were much less likely to progress to T2DM in a new study, but no other diseases were affected.
Daily metformin can stop progression to type 2 diabetes in people with metabolic syndrome, but it does not seem to stall other non-communicable diseases such as cancer and cardiovascular disease.
The “MeMeMe” study, published in Diabetes Care, randomised 1442 people into four groups who received either 1700mg metformin daily (MET), metformin plus Mediterranean diet (MET+MedDiet), Mediterranean diet plus placebo (MedDiet) or placebo only, and followed them for up to five years.
They were all aged 50-79 and all had metabolic syndrome at baseline. The cluster of risk factors including obesity, hypertension, dyslipidaemia and high fasting blood sugar is associated with five times the risk of type 2 diabetes, 2.5 times the risk of cardiovascular mortality and twice the risk of coronary and cerebrovascular diseases, as well as raising the risk for cancers including colorectal and breast, the authors write.
They measured the cumulative incidence of major non-communicable diseases over the follow-up and found dramatic reductions in risk in the two metformin groups – but type 2 diabetes accounted for all of it.
The MET and MET+MedDiet groups had 80% and 92% lower incidence respectively of type 2 diabetes than the MedDiet and placebo groups. The diet added some marginal benefit to metformin but alone was not significantly different from placebo.
There was no significant difference among groups on cancer or CVD.
As a secondary outcome they also compared prevalence of metabolic syndrome and its components across the groups.
The greatest changes were seen in the first year, after which 77.5% of the MET+MedDiet group still had metabolic syndrome, compared with 80% on metformin only, 87% on the diet and 86% on placebo. These all dropped a few more percentage points by the fifth year.
The MET and MET+MedDiet groups had significantly reduced body weight, BMI, waist circumference, waist-to-height ratio and glycaemia compared with placebo.
The MET+MedDiet group also had significantly reduced total and LDL cholesterol.
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The two metformin groups, compared with the two non-metformin groups, improved their weight measures and glycaemia while only the MET+MedDiet groups significantly improved their waist-to-height ratio and cholesterol.
While the MET+MedDiet group had the best results, the differences between the two metformin groups were not significant.
Participants went through a training phase with 500mg daily metformin before randomisation, and those with poor tolerance were excluded. There were 22 dropouts, 19 from the metformin group, all but one because of gastrointestinal effects.
The diet groups were not given strict meal plans but advice on what foods to include and reduce, and were invited to participate in activities such as “thematic kitchen courses, community meals [and] nutritional conferences”.
This is the first study, the authors believe, to show the protective effect of metformin against type 2 diabetes in people with metabolic syndrome.
The Italian authors note their difficulties recruiting patients, since metformin is “not a clinical recommendation” in Italy for anyone without diabetes. GPs even discouraged their patients from joining the trial.
In Australia, metformin is approved as mono or combination therapy for treatment “of type 2 diabetes mellitus in adults, particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycaemic control”, but may be used off-label in pre-diabetes patients.
